|
|
|
| Research progress on anticancer effect and mechanism of isorhamnetin |
| REN Jing1 DAI Qiuqin1 CHEN Ran1 GUAN Chengnong2 LIU Wen1 LI Xiangyong1 |
1.Key Laboratory of Medical Bioactive Molecular Research for Department of Education of Guangdong Province, Guangdong Medical University Institute of Biochemistry and Molecular Biology, Guangdong Medical University Collaborative Innovation Center for Antitumor Active Substance Research and Development, Guangdong Medical University, Guangdong Province, Zhanjiang 524023, China;
2.Department of Oncology, the First Guangdong Affiliated Hospital of Guangdong Medical University, Guangdong Province, Dongguan 523000, China |
|
|
|
Abstract Tumor is still an important factor that threatens human health and increases the social medical burden. The search for plant-derived antitumor drugs with high efficiency and low toxicity is considered to be an important idea for effective treatment and improving the quality of life of tumor patients. Isorhamnetin is a natural small-molecule flavonoid that widely exists in a variety of plants, and has various biological functions such as anti-inflammatory, anti-viral, anti-myocardial hypoxia-ischemia, and lipid-lowering. Recent studies have found that isorhamnetin can act as an anti-tumor drug to exert anti-cancer effects in a variety of tumor cells, and its mechanism of action mainly includes promoting cancer cell apoptosis, inducing cancer cell autophagy, inhibiting its invasion and metastasis, enhance chemotherapy sensitivity, and other processes. This article reviews the anticancer effect and mechanism of isorhamnetin, aiming to provide new ideas and strategies for future research on the anticancer mechanism of isorhamnetin and tumor therapy.
|
|
|
|
|
|
[1] Sung H，Ferlay J，Siegel RL，et al. Global Cancer Statistics 2020：GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries [J]. CA Cancer J Clin，2021，71（3）：209-249.
[2] Gao L，Yao R，Liu Y，et al. Isorhamnetin protects against cardiac hypertrophy through blocking PI3K-AKT pathway [J]. Mol Cell Biochem，2017，429（1/2）：167-177.
[3] Zhao TT，Yang TL，Gong L，et al. Isorhamnetin protects against hypoxia/reoxygenation-induced injure by attenuating apoptosis and oxidative stress in H9c2 cardiomyocytes [J]. Gene，2018，666：92-99.
[4] Kopustinskiene DM，Jakstas V，Savickas A，et al. Flavonoids as Anticancer Agents [J]. Nutrients，2020，12（2）：457.
[5] Gong G，Guan YY，Zhang ZL，et al. Isorhamnetin：A review of pharmacological effects [J]. Biomed Pharmacother，2020， 128：110301.
[6] Hua X，Yu L，You R，et al. Association among Dietary Flavonoids，Flavonoid Subclasses and Ovarian Cancer Risk：A Meta-Analysis [J]. PLoS One，2016，11（3）：e0151134.
[7] Manu KA，Shanmugam MK，Ramachandran L，et al. Isorhamnetin augments the anti-tumor effect of capecitabine through the negative regulation of NF-kappaB signaling cascade in gastric cancer [J]. Cancer Lett，2015，363（1）：28-36.
[8] Wang JL，Quan Q，Ji R，et al. Isorhamnetin suppresses PANC-1 pancreatic cancer cell proliferation through S phase arrest [J]. Biomed Pharmacother，2018，108：925-933.
[9] Ruan Y，Hu K，Chen H. Autophagy inhibition enhances isorhamnetininduced mitochondriadependent apoptosis in nonsmall cell lung cancer cells [J]. Mol Med Rep，2015， 12（4）：5796-5806.
[10] Choi YH. Isorhamnetin induces ROS-dependent cycle arrest at G2/M phase and apoptosis in human hepatocarcinoma Hep3B cells [J]. Gen Physiol Biophys，2019，38（6）：473-484.
[11] Yerlikaya S，Baloglu MC，Diuzheva A，et al. Investigation of chemical profile，biological properties of Lotus corniculatus L. extracts and their apoptotic-autophagic effects on breast cancer cells [J]. J Pharm Biomed Anal，2019，174：286-299.
[12] Duan R，Liang X，Chai B，et al. Isorhamnetin Induces Melanoma Cell Apoptosis via the PI3K/Akt and NF-kappaB Pathways [J]. Biomed Res Int，2020，2020：1057943.
[13] Hu J，Zhang Y，Jiang X，et al. ROS-mediated activation and mitochondrial translocation of CaMKⅡ contributes to Drp1-dependent mitochondrial fission and apoptosis in triple-negative breast cancer cells by isorhamnetin and chloroquine [J]. J Exp Clin Cancer Res，2019，38（1）：225.
[14] Li Q，Ren FQ，Yang CL，et al. Anti-proliferation effects of isorhamnetin on lung cancer cells in vitro and in vivo [J]. Asian Pac J Cancer Prev，2015，16（7）：3035-3042.
[15] Asghar U，Witkiewicz AK，Turner NC，et al. The history and future of targeting cyclin-dependent kinases in cancer therapy [J]. Nat Rev Drug Discov，2015，14（2）：130-146.
[16] Park C，Cha HJ，Choi EO，et al. Isorhamnetin Induces Cell Cycle Arrest and Apoptosis Via Reactive Oxygen Species-Mediated AMP-Activated Protein Kinase Signaling Pathway Activation in Human Bladder Cancer Cells [J]. Cancers （Basel），2019，11（10）：1494.
[17] Zhang HW，Hu JJ，Fu RQ，et al. Flavonoids inhibit cell proliferation and induce apoptosis and autophagy through downregulation of PI3Kgamma mediated PI3K/AKT/mTOR/p70S6K/ULK signaling pathway in human breast cancer cells [J]. Sci Rep，2018，8（1）：11255.
[18] Wei J，Su H，Bi Y，et al. Anti-proliferative effect of isorhamnetin on HeLa cells through inducing G2/M cell cycle arrest [J]. Exp Ther Med，2018，15（4）：3917-3923.
[19] Li C，Yang X，Chen C，et al. Isorhamnetin suppresses colon cancer cell growth through the PI3KAktmTOR pathway [J]. Mol Med Rep，2014，9（3）：935-940.
[20] Ma G，Yang C，Qu Y，et al. The flavonoid component isorhamnetin in vitro inhibits proliferation and induces apoptosis in Eca-109 cells [J]. Chem Biol Interact，2007，167（2）：153-160.
[21] Cai F，Zhang Y，Li J，et al. Isorhamnetin inhibited the proliferation and metastasis of androgen-independent prostate cancer cells by targeting the mitochondrion-dependent intrinsic apoptotic and PI3K/Akt/mTOR pathway [J]. Biosci Rep，2020，40（3）：BSR20192826.
[22] Amaravadi RK，Kimmelman AC，Debnath J. Targeting Autophagy in Cancer：Recent Advances and Future Directions [J]. Cancer Discov，2019，9（9）：1167-1681.
[23] Zhang BY，Wang YM，Gong H，et al. Isorhamnetin flavonoid synergistically enhances the anticancer activity and apoptosis induction by cisplatin and carboplatin in non-small cell lung carcinoma （NSCLC） [J]. Int J Clin Exp Pathol，2015，8（1）：25-37.
[24] Hu S，Huang L，Meng L，et al. Isorhamnetin inhibits cell proliferation and induces apoptosis in breast cancer via Akt and mitogenactivated protein kinase kinase signaling pathways [J]. Mol Med Rep，2015，12（5）：6745-6751.
[25] Shi C，Fan LY，Cai Z，et al. Cellular stress response in Eca-109 cells inhibits apoptosis during early exposure to isorhamnetin [J]. Neoplasma，2012，59（4）：361-369.
[26] Ramachandran L，Manu KA，Shanmugam MK，et al. Isorhamnetin inhibits proliferation and invasion and induces apoptosis through the modulation of peroxisome proliferator-activated receptor gamma activation pathway in gastric cancer [J]. J Biol Chem，2012，287（45）：38028-38040.
[27] Kim JE，Lee DE，Lee KW，et al. Isorhamnetin suppresses skin cancer through direct inhibition of MEK1 and PI3-K [J]. Cancer Prev Res （Phila），2011，4（4）：582-591.
[28] Lee HJ，Lee HJ，Lee EO，et al. Mitochondria-cytochrome C-caspase-9 cascade mediates isorhamnetin-induced apoptosis [J]. Cancer Lett，2008，270（2）：342-353.
[29] Singh M，Yelle N，Venugopal C，et al. EMT：Mechanisms and therapeutic implications [J].Pharmacol Ther，2018， 182：80-94.
[30] Luo W，Liu Q，Jiang N，et al. Isorhamnetin inhibited migration and invasion via suppression of Akt/ERK-mediated epithelial-to-mesenchymal transition （EMT） in A549 human non-small-cell lung cancer cells [J]. Biosci Rep，2019，39（9）：BSR20190159.
[31] Li C，Yang D，Zhao Y，et al. Inhibitory Effects of Isorhamnetin on the Invasion of Human Breast Carcinoma Cells by Downregulating the Expression and Activity of Matrix Metalloproteinase-2/9 [J]. Nutr Cancer，2015，67（7）：1191-200.
[32] Seo S，Seo K，Ki SH，et al. Isorhamnetin Inhibits Reactive Oxygen Species-Dependent Hypoxia Inducible Factor （HIF）-1α Accumulation [J]. Biol Pharm Bull，2016， 39（11）：1830-1838.
[33] Ho GY，Woodward N，Coward JI. Cisplatin versus carboplatin：comparative review of therapeutic management in solid malignancies [J]. Crit Rev Oncol Hematol，2016， 102：37-46.
[34] Manu KA，Shanmugam MK，Li F，et al. Simvastatin sensitizes human gastric cancer xenograft in nude mice to capecitabine by suppressing nuclear factor-kappa B-regulated gene products [J]. J Mol Med （Berl），2014，92（3）：267-276.
[35] Du Y，Jia C，Liu Y，et al. Isorhamnetin Enhances the Radiosensitivity of A549 Cells Through Interleukin-13 and the NF-kappaB Signaling Pathway [J]. Front Pharmacol，2020，11：610772.
[36] Tang SM，Deng XT，Zhou J，et al. Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects [J]. Biomed Pharmacother，2020，121：109604.
[37] Ganai SA，Sheikh FA，Baba ZA，et al. Anticancer activity of the plant flavonoid luteolin against preclinical models of various cancers and insights on different signalling mechanisms modulated [J]. Phytother Res，2021，35（7）：3509-3532. |
|
|
|
