Using Cytochalasins to Improve Current Chemotherapeutic Approaches

Abstract

Although the amount of progress cancer therapy has made in recent years is commendable, considerable limitations still remain. Most agents preferentially target rapidly proliferating cells, thereby destroying tumorigenic growths. Unfortunately, there are many labile cells in the patient that are also rapidly dividing, ultimately perpetuating significant side effects, including immunosuppression. Cytochalasins are microfilament-directed agents most commonly known for their use in basic research to understand cytoskeletal mechanisms. However, such agents also exhibit profound anticancer activity, as indicated by numerous in vitro and in vivo studies. Cytochalasins appear to preferentially damage malignant cells, as shown by their minimal effects on normal epithelial and immune cells. Further, cytochalasins influence the end stages of mitosis, suggesting that such agents could be combined with microtubule-directed agents to elicit a profound synergistic effect on malignant cells. Therefore, it is likely that cytochalasins could be used to supplement current chemotherapeutic measures to improve efficacy rates, as well as decrease the prevalence of drug resistance in the clinical setting.

PU-H71: An improvement on nature's solutions to oncogenic Hsp90 addiction

“…Although there are no microfilament-directed agents currently approved by the FDA or other pharmaceutical regulating bodies, these compounds have intriguing therapeutic potential. Antineoplastic mechanisms of these agents include the potentiation of multinucleated cancer cells that are exquisitely sensitive to other forms of chemotherapy via inhibition of cytokinesis, reducing metastatic potential by limiting cell motility and adhesion (as well as inhibiting the secretion of glucosaminidases), and binding ATPbinding cassette (ABC) transporters, thereby enhancing the activity of other chemotherapeutic agents [1,152,153]. Due to their unique mechanisms of action, microfilament-directed agents have been shown to sensitize malignant cells to mTOR inhibitors, nucleic acid-directed agents and microtubule-directed agents [154][155][156][157][158].…”

“…This is supported by the G 2 /M cell cycle arrest activity observed after Hsp90 inhibition, as concomitant inhibition of mitosis at this critical checkpoint and at cytokinesis would likely reduce the ability of malignant cells to carry out a successful mitotic event. Several microfilamentdirected agents of particular interest include cytochalasins and closely related chaetoglobosins, latrunculins, and jasplakinolide, each of which has been comprehensively described in prior reviews [1,152,159]. Although the synergism between Hsp90 inhibitors and microfilament-directed agents is purely theoretical at this point, preclinical investigation of this concomitant approach could validate potentially novel therapeutic strategies.…”

Preparation, characterization, and cytotoxic effects of liposomal nanoparticles containing cisplatin: an in vitro study

“…They have drawn considerable attention. Liposomal nanoparticles have improved the efficacy of chemotherapeutics and simultaneously reduce their side‐effects …”

The intervention research on treatment by Xianchen to rabbits model of chemotherapeutic phlebitis

“…Another reason is that antineoplastic drugs possess cellular and chemical toxicity 7 . Lastly, the immune system of the patient with tumour is usually compromised and vulnerable to phlebitis 8,9 . Research shows that about 70% of patients develop phlebitis when receiving antineoplastic drugs infusion 1 , which often causes the treatment discontinued.…”