Mechanisms of cancer cell death induction by paclitaxel: an updated review

Zhao, Shuang; Tang, Yufei; Wang, Ruohan; Najafi, Masoud

doi:10.1007/s10495-022-01750-z

Cited by 77 publications

(37 citation statements)

References 236 publications

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“…PTX was first approved for the treatment of ovarian cancer (31), with its application expanding into various other types of cancer some years later (32)(33)(34). To date, it is well known that PTX can induce multiple types of cell death, including mitotic catastrophe, apoptosis, senescence, autophagy and pyroptosis (35). In the present study, it was first observed that A2780 ovarian cancer cells exhibited features of pyroptosis, such as cell swelling, LDH release, deep PI staining and membrane perforation.…”

Section: Discussionmentioning

confidence: 99%

Paclitaxel induces pyroptosis by inhibiting the volume‑sensitive chloride channel leucine‑rich repeat‑containing 8a in ovarian cancer cells

Yang

Liao

et al. 2023

Oncol Rep

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Pyroptosis is a newly identified form of cell death, morphologically characterized by excessive cell swelling. In the present study, paclitaxel (PTX) combined with platinum were used as first-line chemotherapy, against ovarian cancer cells by inducing multiple types of cell death. However, it remains unclear whether PTX can induce pyroptosis in ovarian cancer cells. It was recently reported that PTX inhibited chloride channels, an inhibition known to cause cell swelling. In the present study, it was first verified that pyroptosis-like cell death, as well as cleaved-caspase-3 and cleaved-gasdermin E (GSDME) were induced by PTX in A2780 ovarian cancer cells. PTX inhibited the background-and hypotonicity-activated chloride currents, promoted intracellular chloride ion accumulation, those manifestations are similar to those of the classic volume-regulatory anion channel (VRAC) blocker, 4-(2-butyl-6,7-dichloro-2-cyclopentyl-indan-1-on5-yl) oxobutyric acid (DCPIB). Of note, both DCPIB and the downregulation of VRAC constituent protein leucine-rich repeat-containing 8a themselves could not induce persisted cell swelling and pyroptosis-like phenotypes. However, they could enhance the effects of PTX in inducing pyroptosis-like phenotypes, such as marked cell swelling, cell membrane rupture and excessive activation of caspase-3 and GSDME N-terminal fragment, which ultimately caused marked pyroptosis in A2780 cells. These findings revealed a potential mechanism of PTX and offered new insights into the effects of a synergistical combination of PTX and VRACs blockers in ovarian cancer chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Paclitaxel induces pyroptosis by inhibiting the volume‑sensitive chloride channel leucine‑rich repeat‑containing 8a in ovarian cancer cells

Yang

Liao

et al. 2023

Oncol Rep

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“…TRAIL and FasL can trigger initiation of the extrinsic apoptosis by inducing caspase 8 and/or caspase 10. Granzyme B, perforin and other secretions from NK cells and CTLs, able to perforate cancer cells, lead to cell lysis 60,61 . NK cells and CTLs are able to detect cancer cells through different pathways.…”

Section: Immunoregulatory Effects Of Resveratrol In Tumourmentioning

confidence: 99%

“…Granzyme B, perforin and other secretions from NK cells and CTLs, able to perforate cancer cells, lead to cell lysis. 60,61 NK cells and CTLs are able to detect cancer cells through different pathways.…”

Section: Tumour Immune Microenvironmentmentioning

confidence: 99%

Immunoregulation by resveratrol; implications for normal tissue protection and tumour suppression

Lalani

Fakhari

Radgoudarzi

et al. 2023

Clin Exp Pharma Physio

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Immune reactions are involved in both tumour and normal tissue in response to therapy. Elevated secretion of certain chemokines, exosomes and cytokines triggers inflammation, pain, fibrosis and ulceration among other normal tissue side effects. On the other hand, secretion of tumour-promoting molecules suppresses activity of anticancer immune cells and facilitates the proliferation of malignant cells. Novel anticancer drugs such as immune checkpoint inhibitors (ICIs) boost anticancer immunity via inducing the proliferation of anticancer cells such as natural killer (NK) cells and CD8+ T lymphocytes. Certain chemotherapy drugs and radiotherapy may induce anticancer immunity in the tumour, however, both have severe side effects for normal tissues through stimulation of several immune responses. Thus, administration of natural products with low side effects may be a promising approach to modulate the immune system in both tumour and normal organs. Resveratrol is a well-known phenol with diverse effects on normal tissues and tumours. To date, a large number of experiments have confirmed the potential of resveratrol as an anticancer adjuvant. This review focuses on ensuing stimulation or suppression of immune responses in both tumour and normal tissue after radiotherapy or anticancer drugs. Later on, the immunoregulatory effects of resveratrol in both tumour and normal tissue following exposure to anticancer agents will be discussed.

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“…Taxanes (such as paclitaxel and docetaxel) stabilize microtubules, resulting in multipolar spindles, whereas vinca alkaloids (such as vinblastine and vincristine) inhibit microtubule assembly [ 6 ] ( Figure 4 C). Interestingly, paclitaxel can induce the cell cycle arrest of cancer cells, while senescence may increase the resistance to paclitaxel [ 86 ]. Antiapoptotic members of the Bcl-2 family are often amplified during carcinogenesis, which can lead to a resistance to microtubule inhibitors.…”

Section: Senescence and Bcl-2 Family Proteins In Tetraploid Cellsmentioning

confidence: 99%

Involvement of Bcl-2 Family Proteins in Tetraploidization-Related Senescence

Barriuso

Alvarez-Frutos

Gonzalez-Gutierrez

et al. 2023

IJMS

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The B-cell lymphoma 2 (Bcl-2) family of proteins is the main regulator of apoptosis. However, multiple emerging evidence has revealed that Bcl-2 family proteins are also involved in cellular senescence. On the one hand, the different expression of these proteins determines the entry into senescence. On the other hand, entry into senescence modulates the expression of these proteins, generally conferring resistance to apoptosis. With some exceptions, senescent cells are characterized by the upregulation of antiapoptotic proteins and downregulation of proapoptotic proteins. Under physiological conditions, freshly formed tetraploid cells die by apoptosis due to the tetraploidy checkpoint. However, suppression of Bcl-2 associated x protein (Bax), as well as overexpression of Bcl-2, favors the appearance and survival of tetraploid cells. Furthermore, it is noteworthy that our laboratory has shown that the joint absence of Bax and Bcl-2 antagonist/killer (Bak) favors the entry into senescence of tetraploid cells. Certain microtubule inhibitory chemotherapies, such as taxanes and vinca alkaloids, induce the generation of tetraploid cells. Moreover, the combined use of inhibitors of antiapoptotic proteins of the Bcl-2 family with microtubule inhibitors increases their efficacy. In this review, we aim to shed light on the involvement of the Bcl-2 family of proteins in the senescence program activated after tetraploidization and the possibility of using this knowledge to create a new therapeutic strategy targeting cancer cells.

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Mechanisms of cancer cell death induction by paclitaxel: an updated review

Cited by 77 publications

References 236 publications

Paclitaxel induces pyroptosis by inhibiting the volume‑sensitive chloride channel leucine‑rich repeat‑containing 8a in ovarian cancer cells

Paclitaxel induces pyroptosis by inhibiting the volume‑sensitive chloride channel leucine‑rich repeat‑containing 8a in ovarian cancer cells

Immunoregulation by resveratrol; implications for normal tissue protection and tumour suppression

Involvement of Bcl-2 Family Proteins in Tetraploidization-Related Senescence

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