Loss of mitochondrial membrane potential and caspase activation enhance apoptosis in irradiated K562 cells treated with herbimycin A

Jo, Wol-Soon; Jeong, Min-Ho; Jin, Young‐Hee; Jang, Ji-Yeon; Nam, Byung-Hyouk; Son, Seokhyun; Choi, Seong-Ho; Yoo, Young-Hyun; Kang, Chi‐Dug; Lee, Jae-Dong; Jeong, Soo‐Jin

doi:10.1080/09553000500303773

Cited by 24 publications

(13 citation statements)

References 42 publications

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“…K562 cells treated with radiation and herbimycin A had an accelerated cell death and induced a p53 independent apoptosis. This apoptotic pathway was dependent upon an initial hyperpolarization of the mitochondrial inner membrane, following the release of cytochrome c and subsequent caspase 3 activation [19]. Our results also show the involvement of the caspase‐dependent pathways of apoptosis.…”

Section: Discussionsupporting

confidence: 64%

Radiosensitizing effects of plumbagin in cervical cancer cells is through modulation of apoptotic pathway

Nair

Srinivas

et al. 2007

Molecular Carcinogenesis

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Radiotherapy is the primary line of cancer treatment for cervical cancer and is known to induce cell death in tumors. Radiotherapy is however limited by the total dose that can be given without damaging normal tissue. Plumbagin, a naturally occurring naphthaquinone, has been reported to have free radical producing properties. Hence we hypothesized that plumbagin could also have properties that could modify effects of radiation on cervical cancer cells. Radiation in combination with plumbagin may thus have treatment augmenting effects. Results from our studies have shown that a lower dose of radiation in combination with plumbagin could induce apoptosis more effectively compared to a higher dose of radiation alone. Plumbagin in combination with 2 Gy of radiation was very effective in inducing apoptosis, when compared to a higher radiation dose of 10 Gy alone. This combination also showed a fivefold increase in the activation of caspase 3 in C33A cells. Activation of effector caspases confirms that the induction of apoptosis by irradiation and plumbagin involves caspase‐dependent pathways. Expression of apoptotic regulatory molecules Bcl‐2, Bax and Survivin was also modulated by plumbagin in combination with radiation. In summary, this study shows that a combination of plumbagin and radiation augmented cell growth inhibition compared to higher radiation dose alone, thus indicating that plumbagin may be a potential radiosensitizer acting through the induction of apoptosis. © 2007 Wiley‐Liss, Inc.

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Section: Discussionsupporting

confidence: 64%

Radiosensitizing effects of plumbagin in cervical cancer cells is through modulation of apoptotic pathway

Nair

Srinivas

et al. 2007

Molecular Carcinogenesis

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“…MMP depletion generally precedes apoptotic cell death [31]. However, recent studies underlined a key role of mitochondrial permeability transition pore opening in necrosis and mitotic catastrophe [35, 36]. By treating LoVo cells with IC 50 of CP for 12 and 24 hrs, TMRM fluorescence intensity did not decrease but, in contrast, continuously augmented by increasing exposure times (Fig.…”

Section: Resultsmentioning

confidence: 99%

A novel copper complex induces paraptosis in colon cancer cells via the activation of ER stress signalling

Gandin

Pellei

Tisato³

et al. 2011

J Cellular Molecular Medi

133

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Platinum anticancer drugs have been used for three decades despite their serious side effects and the emerging of resistance phenomena. Recently, a phosphine copper(I) complex, [Cu(thp)4][PF6] (CP), gained special attention because of its strong antiproliferative effects. CP killed human colon cancer cells more efficiently than cisplatin and oxaliplatin and it overcame platinum drug resistance. CP preferentially reduced cancer cell viability whereas non-tumour cells were poorly affected. Colon cancer cells died via a programmed cell death whose transduction pathways were characterized by the absence of hallmarks of apoptosis. The inhibition of 26S proteasome activities induced by CP caused intracellular accumulation of polyubiquitinated proteins and the functional suppression of the ubiquitin–proteasome pathway thus triggering endoplasmic reticulum stress. These data, providing a mechanistic characterization of CP-induced cancer cell death, shed light on the signaling pathways involved in paraptosis thus offering a new tool to overcome apoptosis-resistance in colon cancer cells.

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“…Apoptosis, necrosis, mitotic catastrophe, post-mitotic cell death, and senescence can all contribute to a loss of clonogenicity in heated and irradiated cells (32,33). Mitotic catastrophe events, defined as cell death occurring as a result of a deregulated or failed mitosis (34), can follow loss of Dw m (29). Mitotic catastrophe can be distinguished by formation of multinucleated and/or giant cells (34,35) that contain sub-G 1 DNA (36).…”

Section: Resultsmentioning

confidence: 99%

“…Heat shock-mediated denaturation of key proteins in critical pathways affects many cellular functions. We surveyed several pathways known to be affected by heat shock and irradiation (23)(24)(25)(26)(27)(28)(29). Loss of mitochondrial membrane potential (Dw m ), an important initiator of cell death signaling (30,31), can be a consequence of heat shocks capable of denaturing protein and activating Hsf1 (23).…”

Section: Resultsmentioning

confidence: 99%

Novel Chemical Enhancers of Heat Shock Increase Thermal Radiosensitization through a Mitotic Catastrophe Pathway

et al. 2007

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Radiation therapy combined with adjuvant hyperthermia has the potential to provide outstanding local-regional control for refractory disease. However, achieving therapeutic thermal dose can be problematic. In the current investigation, we used a chemistry-driven approach with the goal of designing and synthesizing novel small molecules that could function as thermal radiosensitizers..2]octan-3-ol was identified as a compound that could lower the threshold for Hsf1 activation and thermal sensitivity. Enhanced thermal sensitivity was associated with significant thermal radiosensitization. We established the structural requirements for activity: the presence of an N-benzenesulfonylindole or N-benzylindole moiety linked at the indolic 3-position to a 2-(1-azabicyclo[2.2.2]octan-3-ol) or 2-(1-azabicyclo[2.2.2]octan-3-one) moiety. These small molecules functioned by exploiting the underlying biophysical events responsible for thermal sensitization. Thermal radiosensitization was characterized biochemically and found to include loss of mitochondrial membrane potential, followed by mitotic catastrophe. These studies identified a novel series of small molecules that represent a promising tool for the treatment of recurrent tumors by ionizing radiation. [Cancer Res 2007;67(2):695-701]

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Loss of mitochondrial membrane potential and caspase activation enhance apoptosis in irradiated K562 cells treated with herbimycin A

Cited by 24 publications

References 42 publications

Radiosensitizing effects of plumbagin in cervical cancer cells is through modulation of apoptotic pathway

Radiosensitizing effects of plumbagin in cervical cancer cells is through modulation of apoptotic pathway

A novel copper complex induces paraptosis in colon cancer cells via the activation of ER stress signalling

Novel Chemical Enhancers of Heat Shock Increase Thermal Radiosensitization through a Mitotic Catastrophe Pathway

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