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Incorporation of natural assumption to deal with cancer

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Abstract

The current state of the art for the use of natural ingredients for cancer therapy is by reviewing the publications and findings associated with cancer research with the employment of flavonoids. Cancer is the most furious disease making fear in the eyes of mankind. Though various treatment methods are prevalent, the patient’s choices are shifting from synthetic treatment strategy to the natural ones. The plant-based metabolites are used very often in our life as a food additive and also as a medicine for primary health care. The safety profile and its efficacy add on advantage for the incorporation of the natural products separately or in combination as a remedy for cancer. Flavonoids, the plant-based metabolites are proven for their anti-inflammatory, anti-oxidant, and anti-cancer properties. Their chemotherapeutic and chemosensitizing power had made it interesting for the researchers to dig more on the health benefits of the flavonoids and incorporating it in a holistic approach, with its natural benefits to relieve the pain and the symptoms of the patient suffering from various medical conditions. The predominant approach for the management of cancer is by following safe and effective treatment modality. In this review, we mentioned the benefits of the flavonoids for the management of various cancers and its potency as a chemotherapeutic agent and as the chemosensitizer. Our mother nature had given remedies to cure various diseases in both human beings and animals by it; we just need to find out the sources and access to them.

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References

  • Abdallah HM, Al-Abd AM, El-Dine RS, El-Halawany AM (2015) P-glycoprotein inhibitors of natural origin as potential tumor chemo-sensitizers: a review. J Adv Res 6(1):45–62

    CAS  Google Scholar 

  • Al-Abd AM, Mahmoud AM, El-Sherbiny GA, El-Moselhy MA, Nofal S, El-Latif HA, El-Shemy HA (2011) Resveratrol enhances the cytotoxic profile of docetaxel and doxorubicin in solid tumour cell lines in vitro. Cell Prolif 44(6):591–601

    CAS  Google Scholar 

  • AL-Samarrai OR, Naji NA, Hameed RR, (2018) Effect of bay leaf (Laurus nobilis L.) and its isolated (flavonoids and glycosides) on the lipids profile in the local Iraqi female rabbits. Tikrit J Pure Sci 22(6):72–75

    Google Scholar 

  • Androutsopoulos VP, Papakyriakou A, Vourloumis D, Tsatsakis AM, Spandidos DA (2010) Dietary flavonoids in cancer therapy and prevention: substrates and inhibitors of cytochrome P450 CYP1 enzymes. Pharmacol Ther 126(1):9–20

    CAS  Google Scholar 

  • Assaraf YG, Brozovic A, Gonçalves AC, Jurkovicova D, Linē A, Machuqueiro M, Saponara S, Sarmento-Ribeiro AB, Xavier CP, Vasconcelos MH (2019) The multi-factorial nature of clinical multidrug resistance in cancer. Drug Resist Updat 46:100645

    Google Scholar 

  • Baliga MS, Jimmy R, Thilakchand KR, Sunitha V, Bhat NR, Saldanha E, Palatty PL (2013) Ocimum sanctum L (Holy Basil or Tulsi) and its phytochemicals in the prevention and treatment of cancer. Nutr Cancer 65(sup1):26–35

    CAS  Google Scholar 

  • Batra P, Sharma AK (2013) Anti-cancer potential of flavonoids: recent trends and future perspectives. 3 Biotech 3(6):439–459

    Google Scholar 

  • Bentz AB (2009) A review of quercetin: Chemistry, antioxidant properties, and bioavailability. J. Young Investig. Available online: http://www.jyi.org/research/re.php?id=3416. Accessed 1 Oct 2013

  • Chen CY, Liu NY, Lin HC, Lee CY, Hung CC, Chang CS (2016) Synthesis and bioevaluation of novel benzodipyranone derivatives as P-glycoprotein inhibitors for multidrug resistance reversal agents. Eur J Med Chem 118:219–229

    CAS  Google Scholar 

  • Chen F, Qin X, Xu G, Gou S, Jin X (2017) Reversal of cisplatin resistance in human gastric cancer cells by a wogonin-conjugated Pt (IV) prodrug via attenuating Casein Kinase 2-mediated Nuclear Factor-κB pathways. Biochem Pharmacol 135:50–68

    CAS  Google Scholar 

  • Cherigo L, Lopez D, Martinez-Luis S (2015) Marine natural products as breast cancer resistance protein inhibitors. Mar Drugs 13(4):2010–2029

    CAS  Google Scholar 

  • Cho HJ, Kim J, Nho CW, Lee KW, Park JHY (2012) Luteolin decreases IGF-II production and downregulates insulin-like growth factor-I receptor signaling in HT-29 human colon cancer cells. BMC Gastroenterol 12(1):9

    Google Scholar 

  • Choudhury H, Pandey M, Gorain B, Chatterjee B, Madheswaran T, Md S, Mak KK, Tambuwala M, Chourasia MK, Kesharwani P (2019) Nanoemulsions as effective carriers for the treatment of lung cancer. In: Nanotechnology-based targeted drug delivery systems for lung cancer. Academic Press, Cambridge, pp 217–247

  • Cianfriglia M (2013) Targeting MDR1-P-glycoprotein (MDR1-Pgp) in immunochemotherapy of acute myeloid leukemia (AML). Ann Ist Super Sanita 49:190–208

    CAS  Google Scholar 

  • Corradini E, Foglia P, Giansanti P, Gubbiotti R, Samperi R, Lagana A (2011) Flavonoids: chemical properties and analytical methodologies of identification and quantitation in foods and plants. Nat Prod Res 25(5):469–495

    CAS  Google Scholar 

  • Correa MG, Couto JS (2016) Anticancer properties of Psidium guajava-a mini-review. Asian Pac J Cancer Prev 17(9):4199–4204

    Google Scholar 

  • Cortés-Rojas DF, de Souza CRF, Oliveira WP (2014) Clove (Syzygium aromaticum): a precious spice. Asian Pac J Trop Biomed 4(2):90–96

    Google Scholar 

  • Cristino L, Bisogno T, Di Marzo V (2019) Cannabinoids and the expanded endocannabinoid system in neurological disorders. Nat Rev Neurol 12:1–21

    Google Scholar 

  • Dai Q, Franke AA, Jin F, Shu XO, Hebert JR, Custer LJ, Zheng W (2002) Urinary excretion of phytoestrogens and risk of breast cancer among Chinese women in Shanghai. Cancer Epidemiol Biomarkers Prev 11(9):815–821

    CAS  Google Scholar 

  • De Angel RE, Blando JM, Hogan MG, Sandoval MA, Lansakara-P DS, Dunlap SM, Cui Z (2013) Stearoyl gemcitabine nanoparticles overcome obesity-induced cancer cell resistance to gemcitabine in a mouse postmenopausal breast cancer model. Cancer Biol Ther 14(4):357–364

    Google Scholar 

  • Eid SY, El-Readi MZ, Fatani SH, Eldin EEMN, Wink M (2015) Natural products modulate the multifactorial multidrug resistance of cancer. Pharmacol Pharm 6(03):146–176

    Google Scholar 

  • Elgart A, Cherniakov I, Aldouby Y, Domb AJ, Hoffman A (2013) Improved oral bioavailability of BCS class 2 compounds by self nano-emulsifying drug delivery systems (SNEDDS): the underlying mechanisms for amiodarone and talinolol. Pharm Res 30(12):3029–3044

    CAS  Google Scholar 

  • Ferreira A, Pousinho S, Fortuna A, Falcão A, Alves G (2015) Flavonoid compounds as reversal agents of the P-glycoprotein-mediated multidrug resistance: biology, chemistry and pharmacology. Phytochem Rev 14(2):233–272

    CAS  Google Scholar 

  • Gadhe CG, Cho SJ (2012) Flavonoids: an emerging lead in the P-glycoprotein inhibition. J Nat Sci 5(2):72–78

    Google Scholar 

  • Geybels MS, Verhage BA, Arts IC, Van Schooten FJ, Goldbohm RA, Van Den Brandt PA (2013) Dietary flavonoid intake, black tea consumption, and risk of overall and advanced stage prostate cancer. Am J Epidemiol 177(12):1388–1398

    Google Scholar 

  • Gonzalez CA, Lujan-Barroso L, Bueno-de-Mesquita HBA, Jenab M, Duell EJ, Agudo A, Teucher B (2012) Fruit and vegetable intake and the risk of gastric adenocarcinoma: a reanalysis of the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST) study after a longer follow-up. Int J Cancer 131(12):2910–2919

    CAS  Google Scholar 

  • Grbčić P, Sedić M (2020) Sphingosine 1-phosphate signaling and metabolism in chemoprevention and chemoresistance in colon cancer. Molecules 25(10):2436

    Google Scholar 

  • Jaganathan SK (2011) Can flavonoids from honey alter multidrug resistance? Med Hypotheses 76(4):535–537

    CAS  Google Scholar 

  • Jaganathan SK, Mandal M (2010) Involvement of non-protein thiols, mitochondrial dysfunction, reactive oxygen species and p53 in honey-induced apoptosis. Investig New Drugs 28(5):624–633

    Google Scholar 

  • Jarosz M, Olbert M, Wyszogrodzka G, Młyniec K, Librowski T (2017) Antioxidant and anti-inflammatory effects of zinc. Zinc-dependent NF-κB signaling. Inflammopharmacology 25(1):11–24

    CAS  Google Scholar 

  • Jiao JW, Wen F (2011) Tanshinone IIA acts via p38 MAPK to induce apoptosis and the down-regulation of ERCC1 and lung-resistance protein in cisplatin-resistant ovarian cancer cells. Oncol Rep 25(3):781–788

    CAS  Google Scholar 

  • Karthika C, Sureshkumar R (2019) Can curcumin along with chemotherapeutic drug and lipid provide an effective treatment of metastatic colon cancer and alter multidrug resistance? Med Hypotheses 132:109325

    CAS  Google Scholar 

  • Karthika C, Suresh Kumar R, Upadhyay D, Janani SK, Vasanthi C, Raja M, NikithaUpathyayula SS (2019) Formulation development and in vitro characterization of solid self-nano emulsifying drug delivery system for curcumin to target colon adenocarcinoma. Med Hypotheses 12(6):3338

    Google Scholar 

  • Karthikeyan S, Laxmanappa Hoti S (2015) Development of fourth generation ABC inhibitors from natural products: a novel approach to overcome cancer multidrug resistance. Anticancer Agents Med Chem 15(5):605–615

    CAS  Google Scholar 

  • Knekt P, Kumpulainen J, Järvinen R, Rissanen H, Heliövaara M, Reunanen A, Aromaa A (2002) Flavonoid intake and risk of chronic diseases. Am J Clin Nutr 76(3):560–568

    CAS  Google Scholar 

  • Kumar R, Sharma S, Prasad D (2018) Acridones: a relatively lesser explored heterocycle for multifactorial diseases. In: Key Heterocycle Cores for Designing Multitargeting Molecules, pp 53–132. https://doi.org/10.1016/B978-0-08-102083-8.00003-0

  • Kunnumakkara AB, Bordoloi D, Padmavathi G, Monisha J, Roy NK, Prasad S, Aggarwal BB (2017) Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases. Br J Pharmacol 174(11):1325–1348

    CAS  Google Scholar 

  • Lee C, Zhang Q, Kozlowski J, Brendler C, Soares MB, Dash A, Mercola D (2013) Natural products and transforming growth factor-beta (TGF-β) signaling in cancer development and progression. Curr Cancer Drug Targets 13(5):500–505

    CAS  Google Scholar 

  • Li X, Hu J, Wang B, Sheng L, Liu Z, Yang S, Li Y (2014) Inhibitory effects of herbal constituents on P-glycoprotein in vitro and in vivo: herb–drug interactions mediated via P-gp. Toxicol Appl Pharmacol 275(2):163–175

    CAS  Google Scholar 

  • Lopes-Rodrigues V, Sousa E, Vasconcelos MH (2016) Curcumin as a modulator of P-glycoprotein in cancer: challenges and perspectives. Pharmaceuticals 9(4):71

    Google Scholar 

  • Lu WD, Qin Y, Yang C, Li L (2013) Effect of curcumin on human colon cancer multidrug resistance in vitro and in vivo. Clinics 68(5):694–701

    Google Scholar 

  • Lu J, Jiang G, Wu Y, Antony S, Meitzler JL, Juhasz A, Liu H, Roy K, Makhlouf H, Chuaqui R, Butcher D (2020) NADPH oxidase 1 is highly expressed in human large and small bowel cancers. PLoS One 15(5):e0233208

    CAS  Google Scholar 

  • Malek SNA, Lee GS, Hong SL, Yaacob H, Wahab NA, Faizal Weber JF, Shah SAA (2011) Phytochemical and cytotoxic investigations of Curcuma mangga rhizomes. Molecules 16(6):4539–4548

    CAS  Google Scholar 

  • Mao Q, Unadkat JD (2015) Role of the breast cancer resistance protein (BCRP/ABCG2) in drug transport—an update. AAPS J 17(1):65–82

    CAS  Google Scholar 

  • Mohana S, Ganesan M, Agilan B, Karthikeyan R, Srithar G, Mary RB, Ambudkar SV (2016) Screening dietary flavonoids for the reversal of P-glycoprotein-mediated multidrug resistance in cancer. Mol BioSyst 12(8):2458–2470

    CAS  Google Scholar 

  • Montanari F, Ecker GF (2015) Prediction of drug–ABC-transporter interaction—recent advances and future challenges. Adv Drug Deliv Rev 86:17–26

    CAS  Google Scholar 

  • Nagula RL, Wairkar S (2019) Recent advances in topical delivery of flavonoids: a review. J Control Release 296:190–201

    CAS  Google Scholar 

  • Neveu V, Perez-Jiménez J, Vos F, Crespy V, du Chaffaut L, Mennen L, Scalbert A (2010) Phenol-Explorer: an online comprehensive database on polyphenol contents in foods. Database. https://doi.org/10.1093/database/bap024

  • Ooko E, Alsalim T, Saeed B, Saeed ME, Kadioglu O, Abbo HS, Efferth T (2016) Modulation of P-glycoprotein activity by novel synthetic curcumin derivatives in sensitive and multidrug-resistant T-cell acute lymphoblastic leukemia cell lines. Toxicol Appl Pharmacol 305:216–233

    CAS  Google Scholar 

  • Panche AN, Diwan AD, Chandra SR (2016) Flavonoids: an overview. J Nutr Sci 5:e47

    CAS  Google Scholar 

  • Phillips JM, Clark C, Herman-Ferdinandez L, Moore-Medlin T, Rong X, Gill JR, Nathan CAO (2011) Curcumin inhibits skin squamous cell carcinoma tumor growth in vivo. Otolaryngol Head Neck Surg 145(1):58–63

    Google Scholar 

  • Prajapati R, Sangamwar AT (2014) Translocation mechanism of P-glycoprotein and conformational changes occurring at drug-binding site: insights from multi-targeted molecular dynamics. Biochim Biophys Acta Biomembr 1838(11):2882–2898

    CAS  Google Scholar 

  • Rajabian A, Rameshrad M, Hosseinzadeh H (2019) Therapeutic potential of Panax ginseng and its constituents, ginsenosides and gintonin, in neurological and neurodegenerative disorders: a patent review. Expert Opin Ther Pat 29(1):55–72

    CAS  Google Scholar 

  • Ramachandran C, Lollett IV, Escalon E, Quirin KW, Melnick SJ (2015) Anticancer potential and mechanism of action of mango ginger (Curcuma amada Roxb.) supercritical CO2 extract in human glioblastoma cells. J Evid Based Complementary Altern Med 20(2):109–119

    Google Scholar 

  • Raman S (2019) Formulation and in-vitro characterization of 5-fluorouracil and flavonoid dual lipid drug conjugates loaded self nanomulsifying drug delivery system for cancer targeting. IJPSR 10(7):3746–3754. https://doi.org/10.13040/IJPSR.0975-8232.10(8).3746-54

  • Ravishankar D, Rajora AK, Greco F, Osborn HM (2013) Flavonoids as prospective compounds for anti-cancer therapy. Int J Biochem Cell Biol 45(12):2821–2831

    CAS  Google Scholar 

  • Rawson NE, Ho CT, Li S (2014) Efficacious anti-cancer property of flavonoids from citrus peels. Food Sci Human Wellness 3(3–4):104–109

    Google Scholar 

  • Roger I, Shipman MA, Symes MD (2017) Earth-abundant catalysts for electrochemical and photoelectrochemical water splitting. Nat Rev Chem 1(1):1–3

    Google Scholar 

  • Sankhalkar S, Vernekar V (2016) Quantitative and qualitative analysis of phenolic and flavonoid content in Moringa oleifera Lam and Ocimum tenuiflorum L. Pharm Res 8(1):16–21

    CAS  Google Scholar 

  • Sato R, Dang KM, McPherson BG, Brown AC (2010) Anticancer activity of guava (Psidium guajava) extracts. J Complement Integr Med 7(1)

  • Shanmugapriya K, Saravana P S, Payal H, Mohammed S, Williams B (2012) Antioxidant potential of pepper (Piper nigrum Linn.) leaves and its antimicrobial potential against some pathogenic microbes. Indian J Nat Prod Resour 3(4):570–577

  • Shen DW, Pouliot LM, Hall MD, Gottesman MM (2012) Cisplatin resistance: a cellular self-defense mechanism resulting from multiple epigenetic and genetic changes. Pharmacol Rev 64(3):706–721

    CAS  Google Scholar 

  • Shukla S, Ohnuma S, Ambudkar SV (2011) Improving cancer chemotherapy with modulators of ABC drug transporters. Curr Drug Targets 12(5):621–630

    CAS  Google Scholar 

  • Srivastava S, Somasagara RR, Hegde M, Nishana M, Tadi SK, Srivastava M, Raghavan SC (2016) Quercetin, a natural flavonoid interacts with DNA, arrests cell cycle and causes tumor regression by activating mitochondrial pathway of apoptosis. Sci Rep 6:24049

    CAS  Google Scholar 

  • Sun L, Chen W, Qu L, Wu J, Si J (2013) Icaritin reverses multidrug resistance of HepG2/ADR human hepatoma cells via downregulation of MDR1 and P-glycoprotein expression. Mol Med Rep 8(6):1883–1887

    CAS  Google Scholar 

  • Sureshkumar R (2018) Plasma glycoprotein efflux induced resistance: implications, mechanism, inhibitors, and novel strategies to overcome. Asian J Pharm 12(04). https://doi.org/10.22377/ajp.v12i04.2834

  • Tang MX, Ogawa K, Asamoto M, Chewonarin T, Suzuki S, Tanaka T, Shirai T (2011) Effects of nobiletin on PhIP-induced prostate and colon carcinogenesis in F344 rats. Nutr Cancer 63(2):227–233

    CAS  Google Scholar 

  • Tsai CC, Lin CS, Hsu CR, Chang CM, Chang IW, Lin LW, Hung CH, Wang JL (2018) Using the Chinese herb Scutellaria barbata against extensively drug-resistant Acinetobacter baumannii infections: in vitro and in vivo studies. BMC Complement Altern Med 18(1):96

    Google Scholar 

  • Verma S (2016) Chemical constituents and pharmacological action of Ocimum sanctum (Indian holy basil-Tulsi). The Journal of Phytopharmacology 5(5):205–207

    Google Scholar 

  • Wei L, Lu N, Dai Q, Rong J, Chen Y, Li Z, Guo Q (2010) Different apoptotic effects of wogonin via induction of H2O2 generation and Ca2+ overload in malignant hepatoma and normal hepatic cells. J Cell Biochem 111(6):1629–1641

    CAS  Google Scholar 

  • Wu CP, Ohnuma S, Ambudkar SV (2011) Discovering natural product modulators to overcome multidrug resistance in cancer chemotherapy. Curr Pharm Biotechnol 12(4):609–620

    CAS  Google Scholar 

  • Xavier CP, Lima CF, Rohde M, Pereira-Wilson C (2011) Quercetin enhances 5-fluorouracil-induced apoptosis in MSI colorectal cancer cells through p53 modulation. Cancer Chemother Pharmacol 68(6):1449–1457

    CAS  Google Scholar 

  • Xia G, Matsidik R, Ablise M, Lei S, Abudula A (2013) Anti-cancer activity of flavonoids from Xinjiang Glycyrrhiza inflata Licorice on proliferation, cytotoxicity and apoptosis in cervical carcinoma cells. J Med Plant Res 7(5):173–178

    Google Scholar 

  • Xiao-ai L, Bei W, Xiao-hong X, Lei P, Bin W, Xiao-xue D, Qi-wei D (2017) Curcumin re-sensitizes multidrug resistant (MDR) breast cancer to cisplatin through inducing autophagy by decreasing CCAT1 expression. RSC Adv 7(53):33572–33579

    Google Scholar 

  • Yashin A, Yashin Y, Xia X, Nemzer B (2017) Antioxidant activity of spices and their impact on human health: A review. Antioxidants 6(3):70

    Google Scholar 

  • Zhang XA, Zhang S, Yin Q, Zhang J (2015) Quercetin induces human colon cancer cells apoptosis by inhibiting the nuclear factor-kappa B Pathway. Pharmacogn Mag 11(42):404–409

    CAS  Google Scholar 

  • Zhang Y, Xu X, Li W, Miao H, Huang S, Zhou Y, Sun Y, Li Z, Guo Q, Zhao L (2016) Activation of endoplasmic reticulum stress and the extrinsic apoptotic pathway in human lung cancer cells by the new synthetic flavonoid, LZ–205. Oncotarget 7(52):87257–87270

    Google Scholar 

  • Zheng J, Zhou Y, Li Y, Xu DP, Li S, Li HB (2016) Spices for prevention and treatment of cancers. Nutrients 8:E495

    Google Scholar 

  • Zhou D, Chen G, Wang J, Li N (2017) Natural cancer chemopreventive reagents from food and herbals. Curr Pharmacol Rep 3(3):138–149

    CAS  Google Scholar 

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Acknowledgments

The authors would like to thank the Department of Science and Technology Fund for improvement of science and technology infrastructure in universities and higher educational institutions (DST-FIST), New Delhi, for their infrastructure support to our department.

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  1. Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, Nilgiris, Tamil Nadu, India

    Chenmala Karthika & Raman Sureshkumar

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  1. Chenmala Karthika
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Dr. R. Sureshkumar: idea for the article and revising the work

Chenmala Karthika: literature survey, data analysis, and manuscript preparation

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Correspondence to Raman Sureshkumar.

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Karthika, C., Sureshkumar, R. Incorporation of natural assumption to deal with cancer. Environ Sci Pollut Res 28, 4902–4917 (2021). https://doi.org/10.1007/s11356-020-11479-4

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