Casticin induces caspase-mediated apoptosis via activation of mitochondrial pathway and upregulation of DR5 in human lung cancer cells

Cancers will continue to be a threat to health unless they can be controlled by combinations of treatment modalities. In this review, evaluate the role of resveratrol (RSV) as a radiosensitizing agent was evaluated and underlying mechanisms holistically explored in different cancer models focusing on therapeutic possibilities. The ability of RSV to modify the effect of radiation exposure in normal and cancer cells has indeed been shown quite convincingly, the combination of RSV and IR exhibiting synergistic effects on different cancer cells. This is relevant since controlled exposure to IR is one of the most frequently applied treatments in cancer patients. However, radiotherapy (XRT) treatment regimes are very often not effective in clinical practice as observed in patients with glioma, prostate cancer (PCa), melanoma, for example, largely due to tumour radioresistant properties. Sensitization of IR-induced apoptosis by natural products such as RSV is likely to be relevant in cancer control and treatment. However, all cancers do not respond to RSV+IR in a similar manner. Therefore, for those such as the radioresistant PCa or melanoma cells, the RSV+IR regime has to be very carefully chosen in order to achieve effective and desirable outcomes with minimum toxicity to normal cells. They are reports that the highest concentration of 100 mM RSV and highest dose of 5 Gy IR are sufficient to kill cells by induction of apoptosis, indicating that RSV is effective in radiosensitizing otherwise radioresistant cells. In general, it has been shown in different cancer cells that RSV+XRT effectively act by enhancing expression of anti-proliferative and pro-apoptotic molecules, and inhibiting pro-proliferative and anti-apoptotic molecules, leading to induction of apoptosis through various pathways, and cell death. If RSV+XRT can suppress the signature of cancer stemness, enhance the radiosensitivity by either targeting the mitochondrial functionality or modulating the tumour necrosis factor-mediated or Fas-FasL-mediated pathways of apoptosis in different cancers, particularly in vivo, its therapeutic use in the control of cancers holds promise in the near future.

Section: Synergistic Effect Of Resveratrol and Radiotherapy In Controsupporting

confidence: 61%

Synergistic Effect of Resveratrol and Radiotherapy in Control of Cancers

Kma

2013

“…It is shown that Res could significantly activated Caspase-3 in a dosedependent manner. Caspases are crucial mediators of programmed cell death (apoptosis) (Zhou et al, 2013). As reported, Caspase-3 is a frequently activated death protease, catalyzing the specific cleavage of many key cellular proteins (Mcllwain et al, 2013).…”

Section: Statistical Analysis and Research Experiencementioning

confidence: 99%

In vitro and in vivo Evaluation of the Antitumor Efficiency of Resveratrol Against Lung Cancer

Yin¹,

Tian²,

L³

et al. 2013

Lung cancer remains a deadly disease with unsatisfactory overall survival. Resveratrol (Res) has the potential to inhibit growth of several types of cancer such as prostate and colorectal examples. In the current study, we evaluated in vitro and in vivo anticancer efficiency of Res in a xenograft model with A549 cells. Cell inhibition effects of Res were measured by MTT assay. Apoptotis of A549 cells was assessed with reference to caspase-3 activity and growth curves of tumor volume and bodyweight of the mice were measured every two days. In vitro cytotoxicity evaluation indicated Res to exert dose-dependent cell inhibition effects against A549 cells with activation of caspase-3. In vivo evaluation showed Res to effectively inhibit the growth of lung cancer in a dosedependent manner in nude mice. Therefore, we believe that Res might be a promising phytomedicine for cancer therapy and further efforts are needed to explore this potential therapeutic strategy.

“…As shown in Figure 1, accumulated data indicate that casticin was isolated from many plant species such as, namely Vitex agnus castus (Choudhary et al, 2009;Mesaik et al, 2009;Webster et al, 2011;Righeschi et al, 2012;Hogner et al, 2013), Daphne genkwa (Xie et al, 2011), Achillea millefolium (Haidara et al, 2006;Csupor-Loffler et al, 2009), Ficus microcarpa , Vitex rotundifolia (Ono et al, 2002;Hu et al, 2007b;Shen et al, 2009;Ye et al, 2010;Koh et al, 2011), Fructus viticis (Hu et al, 2007b;Guan et al, 2010;Chen et al, 2011b;Yang et al, 2011;Zeng et al, 2012;Zhou et al, 2013a), Vitex negundo (Diaz et al, 2003;Kunwar et al, 2010;Velpandian et al, 2013), Crataegus pinnatifida (Kao et al, 2005), Pavetta crassipes (Mali and Dhake, 2011), Nelsonia canescens, Butea frondosa Koen , Dalbergia odorifera (Mali and Dhake, 2011), Bryonia laciniosa (Aggarwal et al, 2011), Citrus unshu (Mali and Dhake, 2011;Nagoor et al, 2011), Centipeda minima (Mali and Dhake, 2011), Clausena excavate (Manosroi et al, 2005), Croton betulaster (de Sampaio e Spohr et al, 2010;Freitas et al, 2011), Dimorphandra mollis (Freitas et al, 2011), Artemisia abrotanum L. (Hernandez et al, 1999), Artemisia annua L …”

Section: Natural Sources Of Casticinmentioning

confidence: 99%

“…Casticin induced early or late apoptosis in a dose dependent manner. Sub-G1 accumulation is usually considered as an apoptotic death profile, this evidence is in sync with mode of cell death and characterized by a set of physiological phenomena, including mitotic catastrophe (Ono et al, 2002;Hu et al, 2007a;Hu et al, 2007b;Shen et al, 2009;Guan et al, 2010;Ye et al, 2010;Chen et al, 2011a;Koh et al, 2011;Zeng et al, 2012;Zhou et al, 2013a) Fructus viticis Chaste tree Mang Jing Zi Fruit Anticancer, inflammation (Hu et al, 2007b;Guan et al, 2010;Chen et al, 2011a;Zeng et al, 2012;Zhou et al, 2013a) Dimorphandra mollis --------Seeds vascular disorders; hypertension (Freitas et al, 2011) Artemisia abrotanum L.…”

Section: 9049 Molecular Mechanisms Of Casticin Action: An Update On mentioning

confidence: 99%

Molecular Mechanisms of Casticin Action: an Update on its Antitumor Functions

Rasul

Zhao²,

Li³

et al. 2014

Casticin (3', 5-dihydroxy-3, 4', 6, 7-tetramethoxyflavone) is an active compound isolated from roots, stems, leaves, fruits and seeds of a variety of plants. It is well known for its pharmacological properties and has been utilized as an anti-hyperprolactinemia, anti-tumor, anti-inflammatory, neuroprotetective, analgesic and immunomodulatory agent. Recently, the anticancer activity of casticin has been extensively investigated. The resulkts showed that it exerts protective potential by targeting apoptosis, considered important for cancer therapies. In this article, our aim was to review the pharmacological and therapeutic applications of casticin with specific emphasis on its anticancer functions and related molecular mechanisms. Chemotherapeutic effects are dependent on multiple molecular pathways, which may provide a new perspective of casticin as a candidate anti-neoplastic drug. This review suggests that additional studies and preclinical trials are required to determine specific intracellular sites of action and derivative targets in order to fully understand the mechanisms of its antitumor activity and validate this compound as a medicinal agent for the prevention and treatment of various cancers.