Microgravity Modulates Drug-Induced Enhancement of Cancer Cell Migration

Prasanth, Devika; Suresh, Sindhuja; Mimlitz, Michael; Zetocha, Noah; Ekpenyong, Andrew

doi:10.1016/j.bpj.2016.11.1687

Cited by 1 publication

(5 citation statements)

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“…This finding of ours supports the increasing attempts to use simulated microgravity as a tool for drug discovery and development [9,10]. Our fourth and fifth findings that microgravity eliminates the significant reduction of the N/C ratio in hydroxyurea treated cells while the paclitaxel treated cells show no such alterations in the N/C ratio in both normal G and in microgravity, extend recent findings that microgravity alters the effects of chemotherapeutic drugs on cancer cell migration [11,12] in a drug-dependent manner. Based on our current data, we make the educated guess that the early nuclear fragmentation caused by paclitaxel at 24 h, both in 1 G and in µg, leads to non-significant changes in the N/C ratio.…”

Section: Discussionsupporting

confidence: 89%

“…It has been shown that microgravity alters the effects of chemotherapeutic drugs on cancer cell migration [ 11 , 12 ]. The alterations were drug-dependent: leukemic cancer cells treated with daunorubicin showed increased chemotactic migration ( p < 0.01) following simulated microgravity (µg) compared to normal gravity on earth (1 G).…”

Section: Introductionmentioning

confidence: 99%

“…The alterations were drug-dependent: leukemic cancer cells treated with daunorubicin showed increased chemotactic migration ( p < 0.01) following simulated microgravity (µg) compared to normal gravity on earth (1 G). But the same cells treated with doxorubicin showed enhanced migration both in 1 G and following µg [ 11 , 12 ]. A different group of researchers replicated the major conclusion (namely, alteration of drug response by microgravity) from these findings [ 11 , 12 ] using doxorubicin and gastric cancer cells [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…But the same cells treated with doxorubicin showed enhanced migration both in 1 G and following µg [ 11 , 12 ]. A different group of researchers replicated the major conclusion (namely, alteration of drug response by microgravity) from these findings [ 11 , 12 ] using doxorubicin and gastric cancer cells [ 13 ]. Remarkably, Rembiałkowska et al found that microgravity increased the chemotherapeutic effect in the case of drug-resistant gastric cancer cells [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…Unsurprisingly, since all these reports [ 11 , 12 , 13 , 14 ] comparing the response of cancer cells to drugs in normal gravity on earth (1 G) versus microgravity conditions are very recent, there is a paucity of such reports in the literature. However, recent literature is replete with findings confirming previously reported changes in single cells, including cancer cells, due to microgravity conditions.…”

Section: Introductionmentioning

confidence: 99%

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Simulated Microgravity-Induced Changes to Drug Response in Cancer Cells Quantified Using Fluorescence Morphometry

McKinley

Taylor

Peeples

et al. 2023

Life

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Unlike plants that have special gravity-sensing cells, such special cells in animals are yet to be discovered. However, microgravity, the condition of apparent weightlessness, causes bone, muscular and immune system dysfunctions in astronauts following spaceflights. Decades of investigations show correlations between these organ and system-level dysfunctions with changes induced at the cellular level both by simulated microgravity as well as microgravity conditions in outer space. Changes in single bone, muscle and immune cells include morphological abnormalities, altered gene expression, protein expression, metabolic pathways and signaling pathways. These suggest that human cells mount some response to microgravity. However, the implications of such adjustments on many cellular functions and responses are not clear. Here, we addressed the question whether microgravity induces alterations to drug response in cancer cells. We used both adherent cancer cells (T98G) and cancer cells in suspension (K562) to confirm the known effects of simulated microgravity and then treated the K562 cells with common cancer drugs (hydroxyurea and paclitaxel) following 48 h of exposure to simulated microgravity via a NASA-developed rotary cell culture system. Through fluorescence-guided morphometry, we found that microgravity abolished a significant reduction (p < 0.01) in the nuclear-to-cytoplasm ratio of cancer cells treated with hydroxyurea. Our results call for more studies on the impact of microgravity on cellular drug response, in light of the growing need for space medicine, as space exploration grows.

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