Moderate Hyperthermia Induces Apoptosis in Metaphase-Arrested Cells But Not in Interphase Hela Cells

Paulson, James R.; Kresch, Agnes Kecskeméti; Mesner, Peter W.

doi:10.4236/abc.2016.63011

Cited by 3 publications

(9 citation statements)

References 46 publications

(45 reference statements)

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“…Multiple attempts have been made to uncover the biological effects of HT on tumors in recent years (1-3). Although the treatment of cancer with HT has been explored in previous studies (4-6), research on the effect of HT alone as a cancer treatment is limited.…”

Section: Introductionmentioning

confidence: 99%

Thermal cycling as a novel thermal therapy to synergistically enhance the anticancer effect of propolis on PANC‑1 cells

Chen

Sun

et al. 2019

Int J Oncol

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Hyperthermia (HT) has shown potential in cancer therapy. In particular, it appears to sensitize cancer cells to chemotherapy. However, a major concern associated with HT is that the thermal dosage applied to the tumor cells may also harm the normal tissue cells. Besides, the drugs used in HT are conventional chemotherapy drugs, which may cause serious side effects. The present study demonstrated a novel methodology in HT therapy called thermal cycle (TC)-HT. With this strategy, a therapeutic window with a maximum synergistic effect was created by combining TC-HT with natural compounds, with minimal unwanted cell damage. The natural compound propolis was selected, and the synergistic anticancer effect of TC-HT and propolis was investigated in pancreatic cancer cells. The present results demonstrated for the first time that TC-HT could enhance the anticancer effect of propolis on PANC-1 cancer cells through the mitochondria-dependent apoptosis pathway and cell cycle arrest. Combined treatment greatly suppressed mitochondrial membrane potential, which is an important indicator of damaged and dysfunctional mitochondria. Furthermore, the cell cycle-regulating protein cell division cycle protein 2 was downregulated upon combined treatment, which prevented cellular progression into mitosis. The present study offers the first report, to the best of our knowledge, on the combination of TC-HT with a natural compound for pancreatic cancer treatment. It is anticipated that this methodology may be a starting point for more sophisticated cancer treatments and may thereby improve the quality of life of many patients with cancer.

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Section: Introductionmentioning

confidence: 99%

Thermal cycling as a novel thermal therapy to synergistically enhance the anticancer effect of propolis on PANC‑1 cells

Chen

Sun

et al. 2019

Int J Oncol

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“…It has been reported that anti-apoptotic proteins like Bcl-2 may be down-regulated by phosphorylation during mitosis [33]. This suggested to us that the differing sensitivity of prometaphase-arrested and interphase H-HeLa cells to hyperthermia [27] may be due to differential activity of Bcl-2 family proteins. Moreover, variations in the activity of these proteins may explain why some HeLa strains are more sensitive to hyperthermia than others.…”

Section: Introductionmentioning

confidence: 75%

“…In previous work, we showed that treatment of prometaphase-arrested H-HeLa cells with mild hyperthermia (39-42°C) led to induction of apoptosis. However, the same treatment did not induce apoptosis in interphase H-HeLa cells or in prometaphase-arrested cells of other HeLa strains [27]. Why do interphase and mitotic cells differ in their sensitivity to hyperthermia?…”

Section: Resultsmentioning

confidence: 97%

“…We have previously reported that apoptosis is rapidly induced when prometaphase-arrested (but not interphase) H-HeLa cells [26] are subjected to mild heat treatment at 39-42°C [27]. This effect was not seen with other HeLa strains tested including for example HeLa S3.…”

Section: Introductionmentioning

confidence: 90%

“…HeLa-MKF-cdk1-as, in which the protein kinase Cdk1 has been made sensitive to the ATP analog 1NM-PP1 [35], was obtained from Dr. Kumiko Samejima, University of Edinburgh. H-HeLa(WML), which is related to but not identical to the H-HeLa used in our previous study [26,27], was obtained from the laboratory of Dr. Ann Palmenberg at the University of Wisconsin-Madison.…”

Section: Hela Cell Culture Cell Cycle Synchronization and Mitotic Arrestmentioning

confidence: 99%

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ABT-263, an Inhibitor of Bcl-2 Family Antiapoptotic Proteins, Sensitizes Prometaphase-Arrested HeLa Cells to Apoptosis Induced by Mild Hyperthermia

Paulson

Luedtke

Suydam

et al. 2022

IJBcRR

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Aims: We have previously shown that mild hyperthermia (39-42°C) rapidly induces apoptosis in H-HeLa cells arrested in mitosis but not in interphase cells and not in mitotic-arrested cells of other HeLa strains such as HeLa S3. Our goal was to test the idea that this sensitivity to hyperthermia is due to down-regulation of Bcl-2 family antiapoptotic proteins during mitosis. Methodology: HeLa S3 cells were arrested in mitosis with spindle poisons and simultaneously treated with mild hyperthermia (42°C) and ABT-263 (Navitoclax), an inhibitor of Bcl-2 and other anti-apoptotic proteins. Apoptosis was observed microscopically and confirmed by observation of procaspase 3 cleavage using western immunoblotting. Results: Treatment of prometaphase-arrested HeLa S3 cells with mild hyperthermia (42°C) and as little as 200 nM ABT-263 induces apoptosis in the great majority of cells within 2 hr, as judged by blebbing of plasma membranes. The effect is not seen with interphase cells and is blocked by caspase inhibitors z-VAD-fmk and z-DEVD-fmk. Conclusion: Our results show that inhibition of Bcl-2 family antiapoptotic proteins sensitizes prometaphase-arrested HeLa cells, but not interphase cells, to apoptosis induced by mild hyperthermia. An open question is why are prometaphase-arrested cells more susceptible than interphase cells? If the features of mitotic-arrested cells that make them sensitive could be identified and mimicked in interphase cells by appropriate drug treatments, it may be possible to combine systemic chemotherapy with local hyperthermia to provide an effective new treatment for tumors.

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The Complex Roles of DNA Repair Pathways, Inhibitors, Hyperthermia, and Contact Inhibition in Cell Cycle Halts

Ahmed

Alghamdi

Islam

et al. 2023

MRMC

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The cell cycle has the capacity to safeguard the cell’s DNA from damage. Thus, cell cycle arrest can allow tumor cells to investigate their own DNA repair processes. Cancer cells become extremely reliant on G1-phase cyclin-dependent kinases due to mutated oncogenes and deactivated tumor suppressors, producing replication stress and DNA damage during the S phase and destroying checkpoints that facilitate progression through the S/G2/M phase. DNA damage checkpoints activate DNA repair pathways to prevent cell proliferation, which occurs when the genome is damaged. However, research on how cells recommence division after a DNA lesion-induced arrest is insufficient which are merely the result of cancer cells’ susceptibility to cell cycle arrest. For example, Defects in the G1 arrest checkpoint may cause a cancer cell to proliferate more aggressively, and attempts to fix these complications may cause the cell to grow more slowly and eventually die. Defects in the G2-M arrest checkpoint may enable a damaged cell to enter mitosis and suffer apoptosis, and attempts to boost the effectiveness of chemotherapy may increase its cytotoxicity. Alternatively, attempts to promote G2-M arrest have also been linked to increased apoptosis in the laboratory. Furthermore, variables, such as hyperthermia, contact inhibition, nucleotide shortage, mitotic spindle damage, and resting phase effects, and DNA replication inhibitors add together to halt the cell cycle. In this review, we look at how nucleotide excision repair, MMR, and other variables, such as DNA replication inhibitors, hyperthermia, and contact inhibition, contribute to the outlined processes and functional capacities that cause cell cycle arrest.

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Moderate Hyperthermia Induces Apoptosis in Metaphase-Arrested Cells But Not in Interphase Hela Cells

Cited by 3 publications

References 46 publications

Thermal cycling as a novel thermal therapy to synergistically enhance the anticancer effect of propolis on PANC‑1 cells

Thermal cycling as a novel thermal therapy to synergistically enhance the anticancer effect of propolis on PANC‑1 cells

ABT-263, an Inhibitor of Bcl-2 Family Antiapoptotic Proteins, Sensitizes Prometaphase-Arrested HeLa Cells to Apoptosis Induced by Mild Hyperthermia

The Complex Roles of DNA Repair Pathways, Inhibitors, Hyperthermia, and Contact Inhibition in Cell Cycle Halts

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